The acute hemodynamic and antiischemic properties of amiodarone were investigated in 16 patients with more than 70% diameter reduction of a left coronary artery. Two successive atrial pacing stress tests (APST I and II) were performed, with an interval of 40 minutes in between, and amiodarone, 5 mg/kg/5 min, was infused 30 minutes after APST I. Hemodynamic changes during amiodarone administration consisted of a 20% decrease in left ventricular (LV) systolic pressure, a 13% decrease in systemic vascular resistance and an 18% decrease in stroke work. Coronary vascular resistance was reduced 19% and coronary sinus flow increased 23%. Despite a secondary 14% increase in heart rate, contractility decreased 21%, accompanied by a 45% increase in LV end-diastolic pressure, which persisted until APST II. Although most hemodynamic changes were observed only during the infusion, contractility and LV systolic pressure were still diminished at the beginning of APST II and remained so during pacing, resulting in a reduction in myocardial oxygen demand compared to APST I. Although overall myocardial oxygen consumption and coronary flow were equal during both pacing tests, amiodarone significantly reduced pacing-induced myocardial ischemia. Lactate metabolism remained normal during APST II (lactate extraction 12 +/- 3% vs -28 +/- 8% (APST I) at maximal pacing rates [p less than 0.05]), while ST-segment depression, LV end-diastolic pressure postpacing and angina were also significantly reduced during APST II. Thus, in humans, intravenous amiodarone reduces vascular resistance and contractility and inhibits pacing-induced myocardial ischemia, presumably by reducing myocardial oxygen demand.